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10 results on '"BRCA-related cancer"'

1. Clinical practice guidelines for BRCA1 and BRCA2 genetic testing.

Author

Pujol, Pascal, Barberis, Massimo, Beer, Philp, Friedman, Eitan, Piulats, Josep M., Capoluongo, Ettore D., Garcia Foncillas, Jesus, Ray-Coquard, Isabelle, Penault-Llorca, Frédérique, Foulkes, William D., Turnbull, Clare, Hanson, Helen, Narod, Steven, Arun, Banu K., Aapro, Matti S., Mandel, Jean-Louis, Normanno, Nicola, Lambrechts, Diether, Vergote, Ignace, and Anahory, Michèle

Subjects
*BREAST tumor risk factors, *PATIENT advocacy, *BRCA genes, *GENETIC testing, *INDIVIDUALIZED medicine, *GERM cells, *ANTINEOPLASTIC agents, *METASTASIS, *MEDICAL protocols, *RISK assessment, *PREVENTIVE health services, *GENOTYPES, *GENETIC counseling, *BREAST tumors, *ONCOLOGISTS, *ENZYME inhibitors, *DISEASE management
Abstract

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices. • Provide update clinical recommendations for BRCA testing for preventive purpose. • Offer testing clinical guidelines for personalised management of early and metatstatic breast cancer. • Actualize germline and tumor testing indications for PARPi-approved therapies. • Address the issues of rapid process and tumor analysis. [ABSTRACT FROM AUTHOR]

Published
2021
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2. Characterization and in silico analyses of the BRCA1/2 variants identified in individuals with personal and/or family history of BRCA-related cancers.

Author

Pirim, Dilek, Kaya, Niyazi, Yıldırım, Elif Uz, Sag, Sebnem Ozemri, and Temel, Sehime Gulsun

Subjects
*FAMILY history (Medicine), *POST-translational modification, *RNA splicing, *BRCA genes, *CANCER
Abstract

Pathogenic variants in the coding regions of the BRCA1/2 lead dysfunctional or nonfunctional BRCA proteins however the contribution of non-coding BRCA1/2 variants to BRCA -related disease risk has not been fully elucidated. Thus, we characterized the functional impact of both coding and non-coding BRCA1/2 variants identified in individuals with personal and/or family history of BRCA-related cancers. The data were produced by resequencing the exons and exon-intron junctions of the BRCA1/2 in 125 individuals and were comprehensively analyzed by using bioinformatics tools and databases. A total of 96 variants (59 coding and 37 non-coding) including 7 novel variants were identified and analyzed for their functional importance. We identified 11 missense variants that potentially affect protein function; 22 variants were likely to alter different types of posttranslational modifications. Also, multiple non-coding BRCA1/2 variants were found to reside in the critical regulatory regions that have the potential to act as eQTLs and affect alternative splicing. The results of our study shed light on the possible contributions of not only coding variants but also non-coding BRCA1/2 variants in BRCRA-related cancers. Further investigation is required to fully understand their potential associations with phenotypes which may ultimately lead their utilization on cancer management as a biomarker. [ABSTRACT FROM AUTHOR]

Published
2020
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3. Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies

Author

Russo, A, Incorvaia, L, Capoluongo, E, Tagliaferri, P, Gori, S, Cortesi, L, Genuardi, M, Turchetti, D, De Giorgi, U, Di Maio, M, Barberis, M, Dessena, M, Del Re, M, Lapini, A, Luchini, C, Jereczek-Fossa, B, Sapino, A, Cinieri, S, Beretta, G, Bella, M, Bracarda, S, Colombo, N, Conteduca, V, Del Mastro, L, Galvano, A, Gristina, V, Guarneri, V, La Verde, N, Lorusso, D, Marchetti, P, Normanno, N, Ottini, L, Pensabene, M, Pignata, S, Procopio, G, Ricevuto, E, Silvestris, N, Tassone, P, Tucci, M, Donato, V, Carrara, S, Paiella, S, Gentilini, O, Gunelli, R, Nicolis, F, Buttitta, F, Colecchia, M, Fassan, M, Malapelle, U, Marchetti, A, Marchio, C, Scarpa, A, Truini, M, Zamboni, G, Gion, M, Trevisiol, C, Gronchi, A, Danesi, R, Di Marco, V, Carrera, P, Ghiorzo, P, Pasini, B, Varesco, L, Artibani, W, Ludovico, G, Campanella, O, Vatrano, S, Tagliafico, E, Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., Tagliafico E., Russo, A, Incorvaia, L, Capoluongo, E, Tagliaferri, P, Gori, S, Cortesi, L, Genuardi, M, Turchetti, D, De Giorgi, U, Di Maio, M, Barberis, M, Dessena, M, Del Re, M, Lapini, A, Luchini, C, Jereczek-Fossa, B, Sapino, A, Cinieri, S, Beretta, G, Bella, M, Bracarda, S, Colombo, N, Conteduca, V, Del Mastro, L, Galvano, A, Gristina, V, Guarneri, V, La Verde, N, Lorusso, D, Marchetti, P, Normanno, N, Ottini, L, Pensabene, M, Pignata, S, Procopio, G, Ricevuto, E, Silvestris, N, Tassone, P, Tucci, M, Donato, V, Carrara, S, Paiella, S, Gentilini, O, Gunelli, R, Nicolis, F, Buttitta, F, Colecchia, M, Fassan, M, Malapelle, U, Marchetti, A, Marchio, C, Scarpa, A, Truini, M, Zamboni, G, Gion, M, Trevisiol, C, Gronchi, A, Danesi, R, Di Marco, V, Carrera, P, Ghiorzo, P, Pasini, B, Varesco, L, Artibani, W, Ludovico, G, Campanella, O, Vatrano, S, Tagliafico, E, Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., and Tagliafico E.

Abstract

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM–AIRO–AISP–ANISC–AURO–Fondazione AIOM–SIAPEC/IAP–SIBioC–SICO–SIF–SIGE–SIGU–SIU–SIURO–UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.

Published
2022

4. Differences in Ovarian and Other Cancers Risks by Population and

Author

Masayuki, Sekine, Koji, Nishino, and Takayuki, Enomoto

Subjects
BRCA2 Protein, Ovarian Neoplasms, animal structures, endocrine system diseases, BRCA1 Protein, risk-reducing salpingo-oophorectomy, Review, hereditary breast and ovarian cancer, female genital diseases and pregnancy complications, BRCA-related cancer, BRCA1/2, Neoplasms, Mutation, Ethnicity, Humans, Female, Genetic Predisposition to Disease, skin and connective tissue diseases
Abstract

Hereditary breast and ovarian cancer is caused by a germline mutation in BRCA1 or BRCA2 genes. The frequency of germline BRCA1/2 gene mutation carriers and the ratio of germline BRCA1 to BRCA2 mutations in BRCA-related cancer patients vary depending on the population. Genotype and phenotype correlations have been reported in BRCA mutant families, however, the correlations are rarely used for individual risk assessment and management. BRCA genetic testing has become a companion diagnostic for PARP inhibitors, and the number of families with germline BRCA mutation identified is growing rapidly. Therefore, it is expected that analysis of the risk of developing cancer will be possible in a large number of BRCA mutant carriers, and there is a possibility that personal and precision medicine for the carriers with specific common founder mutations will be realized. In this review, we investigated the association of ovarian cancer risk and BRCA mutation location, and differences of other BRCA-related cancer risks by BRCA1/2 mutation, and furthermore, we discussed the difference in the prevalence of germline BRCA mutation in ovarian cancer patients. As a result, although there are various discussions, there appear to be differences in ovarian cancer risk by population and BRCA mutation location. If it becomes possible to estimate the risk of developing BRCA-related cancer for each BRCA mutation type, the age at risk-reducing salpingo-oophorectomy can be determined individually. The decision would bring great benefits to young women with germline BRCA mutations.

Published
2021

5. Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

Author

Marion Vandromme, Jean Philippe Spano, Olivier Cussenot, Chloé Rideau, Carole Corsini, Isabelle Treilleux, Michèle Vintraud, Ignace Vergote, Yves-Jean Bignon, Kevin S. Hughes, Bernard Baertschi, Eitan Friedman, Daniel Zarca, Marie Duboys de Labarre, Pascal Pujol, Jean Marc Rey, Joseph Gligorov, Ettore D. Capoluongo, Clarisse Duriez, Marion Imbert-Bouteille, Yann Neuzillet, Jean-Louis Mandel, Isabelle Ray-Coquard, Laurence Gladieff, Jose E. Alés Martínez, Frédérique Penault-Llorca, Karim Fizazi, Pierre Jean Lamy, Julie A. Vendrell, Pascal Hammel, Thibault De La Motte Rouge, Jesus Garcia Foncillas, Diether Lambrechts, Tatiana Kogut-Kubiak, Karen Baudry, William Jacot, William D. Foulkes, Frédéric Thomas, Sophie Nambot, Massimo Barberis, Michèle Anahory, Matti Aapro, Xavier Rebillard, Josep M. Piulats, Florence Duchamp, Steven A. Narod, Sylviane Olschwang, Banu Arun, Marc Bollet, Philp Beer, Clare Turnbull, Helen Hanson, Nicola Normanno, Virginie Galibert, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre de Recherche pour les Pathologies Prostatiques [Paris] (CeRePP), Sorbonne Université (SU), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Gustave Roussy (IGR), Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cancer de Montpellier (ICM), Institut médical d'anayse génomique (IMAGENOME), Labosud, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Centre de Recherches Ecologiques et Evolutives sur le Cancer (MIVEGEC-CREEC), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Léon Bérard [Lyon], Harvard Medical School [Boston] (HMS), Hospital Nuestra Señora de Sonsoles, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Clinique Hartmann [Neuilly-sur-Seine], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncologie gynécologique, Institut Claudius Regaud, AP-HP Hôpital Tenon [Paris], Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP]-Université de Paris (UP), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Massachusetts General Hospital [Boston], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Pujol, P., Barberis, M., Beer, P., Friedman, E., Piulats, J. M., Capoluongo, E. D., Garcia Foncillas, J., Ray-Coquard, I., Penault-Llorca, F., Foulkes, W. D., Turnbull, C., Hanson, H., Narod, S., Arun, B. K., Aapro, M. S., Mandel, J. -L., Normanno, N., Lambrechts, D., Vergote, I., Anahory, M., Baertschi, B., Baudry, K., Bignon, Y. -J., Bollet, M., Corsini, C., Cussenot, O., De la Motte Rouge, T., Duboys de Labarre, M., Duchamp, F., Duriez, C., Fizazi, K., Galibert, V., Gladieff, L., Gligorov, J., Hammel, P., Imbert-Bouteille, M., Jacot, W., Kogut-Kubiak, T., Lamy, P. -J., Nambot, S., Neuzillet, Y., Olschwang, S., Rebillard, X., Rey, J. -M., Rideau, C., Spano, J. -P., Thomas, F., Treilleux, I., Vandromme, M., Vendrell, J., Vintraud, M., Zarca, D., Hughes, K. S., Ales Martinez, J. E., Institut Universitaire de Cancérologie [Paris] (IUC), Service d'urologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, endocrine system diseases, Genetic counseling, Advanced breast, [SDV]Life Sciences [q-bio], BRCA1 and BRCA2 testing, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Guideline, Guidelines, BRCA-related cancer, Càncer de mama, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, medicine, Humans, Genetic Testing, Intensive care medicine, skin and connective tissue diseases, PARP inhibitors, Germ-Line Mutation, Genetic testing, BRCA2 Protein, Ovarian Neoplasms, Adjuvant treatment of cancer, medicine.diagnostic_test, business.industry, BRCA1 Protein, Cancer, medicine.disease, Metastatic breast cancer, 3. Good health, Clinical Practice, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, PARP inhibitor, Practice Guidelines as Topic, Female, Risk assessment, business, Tractament adjuvant del càncer
Abstract

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices. ispartof: EUROPEAN JOURNAL OF CANCER vol:146 pages:30-47 ispartof: location:England status: published

Published
2021
Full Text
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6. BRCA1/2 Variants and Metabolic Factors: Results From a Cohort of Italian Female Carriers

Author

Stefania Tommasi, Bernard Peissel, Siranoush Manoukian, Stefano Magno, Antonella Daniele, Mara Colombo, Paolo Radice, Eleonora Bruno, Daniela Terribile, Patrizia Pasanisi, Andreina Oliverio, Angelo Paradiso, and Donatella Guarino

Subjects
0301 basic medicine, Oncology, Nonsynonymous substitution, Cancer Research, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Logistic regression, lcsh:RC254-282, Article, BRCA-related cancer, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, skin and connective tissue diseases, pathogenic variants, Loss function, business.industry, Insulin, BRCA genes, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Penetrance, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, metabolic factors, business, Ovarian cancer
Abstract

Women carriers of pathogenic variants (mutations) in the BRCA1/2 genes face a high lifetime risk of developing breast cancer (BC) and/or ovarian cancer (OC). However, metabolic factors may influence BRCA penetrance. We studied the association of metabolic factors with BRCA1/2 variants and the risk effect of metabolic exposures in relation to the position of the mutations within the BRCA1/2. Overall, 438 women carriers of BRCA1/2 mutations, aged 18&ndash, 70, with or without a previous diagnosis of BC/OC and without metastases, who joined our randomized dietary trial, were included in the study. The pathogenic variants were divided, according to their predicted effect, into loss of function (LOF) and nonsynonymous variants. The association between metabolic exposures and variants were analyzed by a logistic regression model. LOF variant carriers showed higher levels of metabolic parameters compared to carriers of nonsynonymous variants. LOF variant carriers had significantly higher levels of plasma glucose and serum insulin than nonsynonymous variant carriers (p = 0.03 and p &lt, 0.001, respectively). This study suggests that higher insulin levels are significantly associated with LOF variants. Further investigations are required to explore the association of metabolic factors with LOF variants and the mechanisms by which these factors may affect BRCA-related cancer risk.

Published
2020

7. Differences in Ovarian and Other Cancers Risks by Population and BRCA Mutation Location

Author

Takayuki Enomoto, Koji Nishino, and Masayuki Sekine

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, BRCA1/2, animal structures, endocrine system diseases, Population, QH426-470, Gene mutation, hereditary breast and ovarian cancer, Germline, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, BRCA-related cancer, Internal medicine, Genetics, medicine, skin and connective tissue diseases, education, Genetics (clinical), Genetic testing, education.field_of_study, medicine.diagnostic_test, business.industry, BRCA mutation, risk-reducing salpingo-oophorectomy, Cancer, medicine.disease, female genital diseases and pregnancy complications, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), business
Abstract

Hereditary breast and ovarian cancer is caused by a germline mutation in BRCA1 or BRCA2 genes. The frequency of germline BRCA1/2 gene mutation carriers and the ratio of germline BRCA1 to BRCA2 mutations in BRCA-related cancer patients vary depending on the population. Genotype and phenotype correlations have been reported in BRCA mutant families, however, the correlations are rarely used for individual risk assessment and management. BRCA genetic testing has become a companion diagnostic for PARP inhibitors, and the number of families with germline BRCA mutation identified is growing rapidly. Therefore, it is expected that analysis of the risk of developing cancer will be possible in a large number of BRCA mutant carriers, and there is a possibility that personal and precision medicine for the carriers with specific common founder mutations will be realized. In this review, we investigated the association of ovarian cancer risk and BRCA mutation location, and differences of other BRCA-related cancer risks by BRCA1/2 mutation, and furthermore, we discussed the difference in the prevalence of germline BRCA mutation in ovarian cancer patients. As a result, although there are various discussions, there appear to be differences in ovarian cancer risk by population and BRCA mutation location. If it becomes possible to estimate the risk of developing BRCA-related cancer for each BRCA mutation type, the age at risk-reducing salpingo-oophorectomy can be determined individually. The decision would bring great benefits to young women with germline BRCA mutations.

Published
2021
Full Text
View/download PDF

8. Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies.

Author

Russo A, Incorvaia L, Capoluongo E, Tagliaferri P, Gori S, Cortesi L, Genuardi M, Turchetti D, De Giorgi U, Di Maio M, Barberis M, Dessena M, Del Re M, Lapini A, Luchini C, Jereczek-Fossa BA, Sapino A, and Cinieri S

Subjects
Female, Humans, Italy, Male, Societies, Scientific, Ovarian Neoplasms diagnosis, Ovarian Neoplasms genetics, Ovarian Neoplasms prevention & control, Pancreatic Neoplasms, Prostatic Neoplasms diagnosis, Prostatic Neoplasms genetics, Prostatic Neoplasms therapy
Abstract

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM-AIRO-AISP-ANISC-AURO-Fondazione AIOM-SIAPEC/IAP-SIBioC-SICO-SIF-SIGE-SIGU-SIU-SIURO-UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations., Competing Interests: Disclosure LC: honoraria for presentations from Astra Zeneca, Pfizer, Novartis, MSD; support for attending meetings from AstraZeneca; advisory board of Astra Zeneca, Novartis, MSD, Gilead. UDG: consulting fees from AstraZeneca, Pfizer, MSD, BMS, Ipsen, Novartis, Astellas, Janssen, Bayer, PharmaMar, Eisai, and Clovis. MDM: grants from any entity from Tesaro, GlaxoSmithKline; consulting fees from Novartis, Roche, AstraZeneca, Merck Serono, Pfizer, Merck Sharp & Dohme, Janssen, Eisai, Takeda, Boehringer Ingelheim, and Servier; honoraria for presentations from Novartis, Roche, AstraZeneca, Pfizer, Merck Sharp & Dohme, Janssen, Astellas, Boehringer Ingelheim; serves on the advisory board of Merck Sharp & Dohme, Amgen, Janssen, and Astellas. MG: honoraria for presentations from MSD. BAJF: honoraria for presentations from Janssen, Ferring, Bayer, Roche, Astellas, Elekta, Carl Zeiss, Ipsen, Accuray, and IBA. AL: consulting fees from Astellas, Jansen, and Bayer. AR: advisory boards of Bristol, Pfizer, Bayer, Kyowa Kirin, Ambrosetti; and honoraria for presentations from Roche Diagnostic and AstraZeneca. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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9. BRCA1/2 Variants and Metabolic Factors: Results From a Cohort of Italian Female Carriers.

Author

Oliverio, Andreina, Bruno, Eleonora, Colombo, Mara, Paradiso, Angelo, Tommasi, Stefania, Daniele, Antonella, Terribile, Daniela Andreina, Magno, Stefano, Guarino, Donatella, Manoukian, Siranoush, Peissel, Bernard, Radice, Paolo, and Pasanisi, Patrizia

Subjects
*TUMOR risk factors, *BLOOD sugar, *GENETICS, *INSULIN, *METABOLIC disorders, *GENETIC mutation, *PROTEINS, *WOMEN, *LOGISTIC regression analysis, *BRCA genes, *GENETIC carriers, *DISEASE complications
Abstract

Simple Summary: Women who inherit a BRCAmutation face a high lifetime risk of developing cancer. However, several factors, genetic and/or "environmental", may influence BRCA penetrance. We studied in 438 women carriers of BRCA1/2 the association of metabolic factors with BRCA1/2 variants and the risk effect of metabolic exposures in relation to the position of the mutations within the BRCA1/2. The pathogenic variants were divided into loss of function (LOF) and nonsynonymous variants. Findings from this study suggest that higher insulin levels are significantly associated with BRCA LOF variants compared to nonsynonymous variant carriers. Therefore, our results support the hypothesis that the impairment of BRCA protein functions could result in a different association with "metabolic" factors, possibly due to a genetic effect on the etiology of altered response to metabolism. Women carriers of pathogenic variants (mutations) in the BRCA1/2 genes face a high lifetime risk of developing breast cancer (BC) and/or ovarian cancer (OC). However, metabolic factors may influence BRCA penetrance. We studied the association of metabolic factors with BRCA1/2 variants and the risk effect of metabolic exposures in relation to the position of the mutations within the BRCA1/2. Overall, 438 women carriers of BRCA1/2 mutations, aged 18–70, with or without a previous diagnosis of BC/OC and without metastases, who joined our randomized dietary trial, were included in the study. The pathogenic variants were divided, according to their predicted effect, into loss of function (LOF) and nonsynonymous variants. The association between metabolic exposures and variants were analyzed by a logistic regression model. LOF variant carriers showed higher levels of metabolic parameters compared to carriers of nonsynonymous variants. LOF variant carriers had significantly higher levels of plasma glucose and serum insulin than nonsynonymous variant carriers (p = 0.03 and p < 0.001, respectively). This study suggests that higher insulin levels are significantly associated with LOF variants. Further investigations are required to explore the association of metabolic factors with LOF variants and the mechanisms by which these factors may affect BRCA-related cancer risk. [ABSTRACT FROM AUTHOR]

Published
2020
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10. Lifestyle Characteristics in Women Carriers of BRCA Mutations: Results From an Italian Trial Cohort.

Author

Bruno E, Oliverio A, Paradiso A, Daniele A, Tommasi S, Terribile DA, Filippone A, Digennaro M, Pilato B, Danza K, Guarino D, Rossi C, Rossi MM, Venturelli E, Giussani M, Peissel B, and Pasanisi P

Subjects
Adult, Aged, BRCA1 Protein, BRCA2 Protein, Body Mass Index, Breast Neoplasms genetics, Cohort Studies, Female, Humans, Italy, Middle Aged, Prospective Studies, Breast Neoplasms prevention & control, Life Style, Nutritional Status, Physical Fitness
Abstract

Background: Women with deleterious mutations in BRCA1/2 have a high lifetime penetrance of developing breast cancer and/or ovarian cancer. Genetic and/or environmental factors may influence BRCA penetrance, and identifying modifiable exposures might be valuable for prevention., Patients and Methods: We implemented a multicenter prospective 2-arm (1:1) randomized controlled trial to investigate whether a Mediterranean dietary intervention with moderate protein restriction would reduce potential modulators of BRCA penetrance such as insulin-like growth factor 1 (IGF-1), body weight, and metabolic risk factors. We studied the baseline characteristics of women with BRCA-positive disease who joined the trial cohort, focusing on the relationships between selected lifestyle exposures, metabolic/anthropometric parameters, and BRCA-related cancer., Results: A total of 502 women (304 with a previous diagnosis of breast cancer and/or ovarian cancer and 198 unaffected) with deleterious BRCA mutations, with or without a previous cancer, aged 18 to 70 years and without metastases were included. Late age at menarche and pregnancy were negatively associated with BRCA-related cancer, especially in women with BRCA1-positive disease. Higher fat mass and the presence of 4 or 5 metabolic risk factors were significantly associated with BRCA-related cancer (hazard ratio, 1.87, 95% confidence interval, 1.21-2.88; and hazard ratio, 1.87, 95% confidence interval, 1.11-3.19, respectively), with greater effect in BRCA2-positive women., Conclusions: Our findings confirm previous observations about reproductive factors in women with BRCA disease and suggest a potential impact of metabolic factors in BRCA-related cancer. The prospective follow-up of the trial cohort will enable us to study the environmental modulators of BRCA penetrance and their impact in relation to the history of BRCA-related cancer. [ClinicalTrials.gov NCT03066856]., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2021
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